Daniel Natera-de Benito1, A Reghan Foley2, Cristina Domínguez-González2, Carlos Ortez2, Minal Jain2, Aron Mebrahtu2, Sandra Donkervoort2, Ying Hu2, Margaret Fink2, Pomi Yun2, Tracy Ogata2, Julita Medina2, Meritxell Vigo2, Katherine G Meilleur2, Meganne E Leach2, Jahannaz Dastgir2, Jordi Díaz-Manera2, Laura Carrera-García2, Jessica Expósito-Escudero2, Macarena Alarcon2, Daniel Cuadras2, Elena Montiel-Morillo2, José C Milisenda2, Raul Dominguez-Rubio2, Montse Olivé2, Jaume Colomer2, Cristina Jou2, Cecilia Jimenez-Mallebrera2, Carsten G Bönnemann2, Andres Nascimento2. 1. From the Neuromuscular Unit (D.N.-d.B., C.O., L.C.-G., J.E.-E., M.A., J.C., C.J., C.J.-M., A.N.), Neuropaediatrics Department, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona; Center for the Biomedical Research on Rare Diseases (CIBERER), ISCIII, Spain; Neuromuscular and Neurogenetic Disorders of Childhood Section (A.R.F., S.D., Y.H., M.F., P.Y., T.O., M.E.L., J.D., C.G.B.), National Institute of Neurological Disorders and Stroke, Rehabilitation Medicine Department (M.J., A.M.), Clinical Research Center, and Neuromuscular Symptoms Unit (K.G.M.), Tissue Injury Branch, National Institute of Nursing Research, NIH, Bethesda, MD; Department of Neurology (C.D.-G., E.M.-M.), Hospital Universitario 12 de Octubre, Research Institute (imas12), Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Department of Rehabilitation and Physical Medicine (J.M., M.V.), Hospital Sant Joan de Deu, Barcelona, Spain; Neuromuscular Diseases Unit (J.D.-M.), Department of Neurology, Hospital de La Santa Creu i Sant Pau, Universitat Autònoma de Barcelona and Centre for Biomedical Network Research on Rare Diseases (CIBERER); Statistics Department (D.C.), Fundació Sant Joan de Déu; Department of Internal Medicine (J.C.M.), Hospital Clinic, Universitat de Barcelona and CIBERER, Villarroel 170; Neuropathology Unit (R.D.-R., M.O.), Department of Pathology and Neuromuscular Unit, IDIBELL-Hospital Universitari de Bellvitge, Barcelona, Spain; and Department of Pathology (C.J.), Hospital Sant Joan de Déu, Barcelona, Spain. dnatera@sjdhospitalbarcelona.org. 2. From the Neuromuscular Unit (D.N.-d.B., C.O., L.C.-G., J.E.-E., M.A., J.C., C.J., C.J.-M., A.N.), Neuropaediatrics Department, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona; Center for the Biomedical Research on Rare Diseases (CIBERER), ISCIII, Spain; Neuromuscular and Neurogenetic Disorders of Childhood Section (A.R.F., S.D., Y.H., M.F., P.Y., T.O., M.E.L., J.D., C.G.B.), National Institute of Neurological Disorders and Stroke, Rehabilitation Medicine Department (M.J., A.M.), Clinical Research Center, and Neuromuscular Symptoms Unit (K.G.M.), Tissue Injury Branch, National Institute of Nursing Research, NIH, Bethesda, MD; Department of Neurology (C.D.-G., E.M.-M.), Hospital Universitario 12 de Octubre, Research Institute (imas12), Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain; Department of Rehabilitation and Physical Medicine (J.M., M.V.), Hospital Sant Joan de Deu, Barcelona, Spain; Neuromuscular Diseases Unit (J.D.-M.), Department of Neurology, Hospital de La Santa Creu i Sant Pau, Universitat Autònoma de Barcelona and Centre for Biomedical Network Research on Rare Diseases (CIBERER); Statistics Department (D.C.), Fundació Sant Joan de Déu; Department of Internal Medicine (J.C.M.), Hospital Clinic, Universitat de Barcelona and CIBERER, Villarroel 170; Neuropathology Unit (R.D.-R., M.O.), Department of Pathology and Neuromuscular Unit, IDIBELL-Hospital Universitari de Bellvitge, Barcelona, Spain; and Department of Pathology (C.J.), Hospital Sant Joan de Déu, Barcelona, Spain.
Abstract
OBJECTIVE: To accurately categorize the phenotypes of individuals with collagen VI-related dystrophies (COL6-RDs) during the first years of life to predict long-term motor function and pulmonary function, to provide phenotype-specific anticipatory care, and to improve clinical trial readiness. METHODS: This retrospective, multicenter, international study analyzed the relationship of long-term motor and pulmonary function with the initial maximal motor ability achieved in individuals with COL6-RD. RESULTS: We studied 119 patients with COL6-RD from Spain (n = 54) and the United States (n = 65). The early maximal motor milestones of ability to rise from the floor unassisted and ability to climb 4 steps without holding onto a railing demonstrated reliability in distinguishing between 3 COL6-RD phenotypic subgroups: (1) Ullrich congenital muscular dystrophy, (2) intermediate COL6-RD, and (3) Bethlem myopathy. Long-term motor function and pulmonary function are strongly correlated with the maximal motor ability achieved during the first years of life. Maximal motor capacity can predict other disease-relevant events such as the age at loss of ambulation and the need for the initiation of nocturnal noninvasive ventilation. CONCLUSION: This work proposes a prospective phenotypic classification for COL6-RDs that will enable an accurate prediction of a patient's COL6-RD phenotype during the first years of life. The ability to establish a patient's COL6-RD phenotypic classification early will enable a more accurate prognosis of future motor and pulmonary function, thus improving anticipatory clinical care, and it will be instrumental in aiding the design of future clinical trials by allowing early stratification of trial cohorts.
OBJECTIVE: To accurately categorize the phenotypes of individuals with collagen VI-related dystrophies (COL6-RDs) during the first years of life to predict long-term motor function and pulmonary function, to provide phenotype-specific anticipatory care, and to improve clinical trial readiness. METHODS: This retrospective, multicenter, international study analyzed the relationship of long-term motor and pulmonary function with the initial maximal motor ability achieved in individuals with COL6-RD. RESULTS: We studied 119 patients with COL6-RD from Spain (n = 54) and the United States (n = 65). The early maximal motor milestones of ability to rise from the floor unassisted and ability to climb 4 steps without holding onto a railing demonstrated reliability in distinguishing between 3 COL6-RD phenotypic subgroups: (1) Ullrich congenital muscular dystrophy, (2) intermediate COL6-RD, and (3) Bethlem myopathy. Long-term motor function and pulmonary function are strongly correlated with the maximal motor ability achieved during the first years of life. Maximal motor capacity can predict other disease-relevant events such as the age at loss of ambulation and the need for the initiation of nocturnal noninvasive ventilation. CONCLUSION: This work proposes a prospective phenotypic classification for COL6-RDs that will enable an accurate prediction of a patient's COL6-RD phenotype during the first years of life. The ability to establish a patient's COL6-RD phenotypic classification early will enable a more accurate prognosis of future motor and pulmonary function, thus improving anticipatory clinical care, and it will be instrumental in aiding the design of future clinical trials by allowing early stratification of trial cohorts.
Authors: Véronique Bolduc; A Reghan Foley; Herimela Solomon-Degefa; Apurva Sarathy; Sandra Donkervoort; Ying Hu; Grace S Chen; Katherine Sizov; Matthew Nalls; Haiyan Zhou; Sara Aguti; Beryl B Cummings; Monkol Lek; Taru Tukiainen; Jamie L Marshall; Oded Regev; Dina Marek-Yagel; Anna Sarkozy; Russell J Butterfield; Cristina Jou; Cecilia Jimenez-Mallebrera; Yan Li; Corine Gartioux; Kamel Mamchaoui; Valérie Allamand; Francesca Gualandi; Alessandra Ferlini; Eric Hanssen; Steve D Wilton; Shireen R Lamandé; Daniel G MacArthur; Raimund Wagener; Francesco Muntoni; Carsten G Bönnemann Journal: JCI Insight Date: 2019-03-21
Authors: E M Clement; L Feng; R Mein; C A Sewry; S A Robb; A Y Manzur; E Mercuri; C Godfrey; T Cullup; S Abbs; F Muntoni Journal: Neuromuscul Disord Date: 2012-04-03 Impact factor: 4.296
Authors: M Okada; G Kawahara; S Noguchi; K Sugie; K Murayama; I Nonaka; Y K Hayashi; I Nishino Journal: Neurology Date: 2007-09-04 Impact factor: 9.910
Authors: N Deconinck; P Richard; V Allamand; A Behin; P Lafôret; A Ferreiro; A de Becdelievre; C Ledeuil; C Gartioux; I Nelson; R Y Carlier; P Carlier; K Wahbi; N Romero; M T Zabot; F Bouhour; V Tiffreau; A Lacour; B Eymard; T Stojkovic Journal: J Neurol Neurosurg Psychiatry Date: 2014-12-22 Impact factor: 10.154